Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer
Authors: Ying Cheng, Liang Han, Lin Wu, Jun Chen, Hongmei Sun, Guilan Wen, Yinghua Ji, Mikhail Dvorkin, Jianhua Shi, Zhijie Pan, Jinsheng Shi, Xicheng Wang, Yuansong Bai, Tamar Melkadze, Yueyin Pan, Xuhong Min, Maksym Viguro, Xingya Li, Yanqiu Zhao, Junquan Yang, Tamta Makharadze, Ekaterine Arkania, Wenying Kang, Qingyu Wang, Jun Zhu, Xiubao Ren, Vladimer Kuchava, Guoping Sun, Gaofeng Li, Wen Lin, Tao Zhang, Hakan Harputluoglu, Irfan Cicin, Guosheng Feng, Yanrong Hao, Kejing Ying, Ping Sun, Aihong Zhong, Guangyu An, Yan Wang, Chun Chen, Sheng Yang, Zhendong Chen, Konstantin Penkov, Yuriy Semegen, Oleg Kobziev, Feng Luo, Peiguo Cao, Zhixiong Yang, Min Fan, Wen Li, Robert Mroz, Andrey Akopov, Tuncay Goksel, Mahmut Gumus, Wenlei Zhuo, Jian Fang, Hui Zhao, Zhong Lin, Yanping Hu, Yarong Li, Shuqun Zhang, Jiuwei Cui, Nadezhda Kovalenko, Cagatay Arslan, Devrim Cabuk, Alev Türker, Igor Bondarenko, Yevhen Hotko, Olexandr Goloborodko, Dongji Chen, Mengzhao Wang, Zhuang Yu, Junguo Lu, Liyan Jiang, Hao Xiong, Davit Giorgadze, Sergey Orlov, Ahmet Bilici, Ivan Sinelnikov, Gongyan Chen, Lu Yue, Xiaoli Zhu, Liqin Lu, Mariam Zhvania, Malgorzata Ulanska, Igor Lifirenko, Timur Andabekov, Maria Smagina, Fedor Moiseenko, Yuksel Urun, Ligong Nie, Bangwei Cao, Zhenyu You, Haixin Huang, Shenpeng Ying, Alexandre Tavartkiladze, Tariel Kitiashvili, Amiran Matitashvili, Tsira Kortua, Eugeny Kulikov, Sergey Cheporov, Vadim Shirinkin, Mustafa Ozguroglu, Mehmet Artac, Oleksii Kolesnik, Andrii Gardashnikov, Denys Pominchuk
Journal: JAMA (2022)

Importance Programmed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC. Objective To evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC. Design, Setting, and Participants This international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021. Interventions Patients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks. Main Outcomes and Measures The primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P &amp;amp;lt; .012). There were 13 secondary outcomes, including progression-free survival and adverse events. Results Among the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months-not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0-14.3 months]) (hazard ratio, 0.63 [95% CI, 0.49-0.82]; P &amp;amp;lt; .001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5-6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2-4.5 months]) (hazard ratio, 0.48 [95% CI, 0.38-0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group. Conclusions and Relevance Among patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population. Trial Registration ClinicalTrials.gov Identifier: NCT04063163